title: Design and synthesis of novel series of 5-HT6 receptor ligands having indole, a central aromatic core and 1-amino-4 methyl piperazine as a positive ionizable group.
abstract: The exclusive distribution of 5-HT6 receptor in the brain regions and high affinity for antipsychotic and antidepressant drugs makes 5-HT6 receptor a promising target in treatment of CNS diseases. Based on a pharmacophore model reported in the literature, we designed and synthesized a novel series of 5-HT6 receptor ligands having indole as a central aromatic core and 1-amino-4-methyl piperazine as positive ionizable group. Out of 32 compounds we have successfully identified 10 new compounds as 5-HT6 receptor antagonists. The structure-activity relationship (SAR) studies have been carried out by mapping the compounds with the 3D QSAR model.
authors.affiliation: College of Pharmacy and Division of Life and Pharmaceutical Sciences, Ewha Womans University, Seoul 120-750, Republic of Korea.
authors.forename: Faisal
authors.initials: F
authors.lastname: Hayat
authors.forename: Sungjin
authors.initials: S
authors.lastname: Cho
authors.forename: Hyewhon
authors.initials: H
authors.lastname: Rhim
authors.forename: Ambily Nath
authors.initials: AN
authors.lastname: Indu Viswanath
authors.forename: Ae Nim
authors.initials: AN
authors.lastname: Pae
authors.forename: Jae Yeol
authors.initials: JY
authors.lastname: Lee
authors.forename: Dong Joon
authors.initials: DJ
authors.lastname: Choo
authors.forename: Hea-Young Park
authors.initials: HY
authors.lastname: Choo
mesh_terms: D000465:Algorithms; D015195:Drug Design; D057809:HEK293 Cells; D006801:Humans; D007211:Indoles / Q000737:chemistry*; D007477:Ions / Q000737:chemistry; D008024:Ligands; D000077489:Piperazine; D010879:Piperazines / Q000737:chemistry*; D011485:Protein Binding; D021281:Quantitative Structure-Activity Relationship; D011985:Receptors, Serotonin / Q000737:chemistry* / Q000235:genetics / Q000378:metabolism; D011994:Recombinant Proteins / Q000096:biosynthesis / Q000737:chemistry / Q000235:genetics; D012702:Serotonin Antagonists / Q000138:chemical synthesis* / Q000737:chemistry / Q000378:metabolism; D013329:Structure-Activity Relationship
chemical_list: D007211:Indoles; D007477:Ions; D008024:Ligands; D010879:Piperazines; D011985:Receptors, Serotonin; D011994:Recombinant Proteins; D012702:Serotonin Antagonists; C097216:serotonin 6 receptor; D000077489:Piperazine; C030374:indole
keywords: 1-Amino-4-methylpiperazine; 3D QSAR; 5-HT(6) receptor antagonist; Pharmacophore mapping; Sulfonyl indole